b型流感嗜血杆菌结合疫苗免疫后血清抗Hib PRP IgG抗体的免疫应答

Immunogenicity of Hib-TT conjugate vaccine in 6-59 months.old young children and the antibody persistence in 3-5 months-old infants after primary and boosting injection with Hib-TT and Act.Hib conjugate vaccines

目的评价兰州生物制品研究所生产的Hib—TY结合疫苗的免疫原性。方法采用随机、开放的对照研究方法，对6～59月龄儿童分别接种2或1剂实验疫苗，观察免疫后1个月时受试者血清抗HibPRPIgG抗体几何平均浓度（GMC）和抗体浓度≥1．0μg／ml的比例；将3—5月龄198名婴幼儿随机分为两组分别接种3剂实验疫苗或对照疫苗结合疫苗，基础免疫后1年时分别给予1剂加强免疫。观察基础免疫后1个月、1年、加强免疫后1个月和1年时血清抗HibPRPIgG抗体GMC和抗体浓度≥1．0μg／ml的受试者比例。结果给6—59月龄健康受试者接种疫苗1个月后，至少有91％以上受试者血清抗HibPRPIgG抗体浓度≥1．0μg／ml；其中6～11月龄组2剂免疫后血清抗体GMC为14．04μg／m1（95％CI：12．40—15．90），所有受试者血清抗体浓度均≥1．0μg／ml；12～59月龄幼儿组1剂免疫后血清抗体GMC为14．01μg/ml（95％CI：12．99～15．11），至少有91．30％（95％CI：86．34～94．98）的受试者血清抗体浓度≥1．0μg／ml。3—5月龄婴幼儿经3剂试验疫苗接种后血清抗体GMC为14．52μg／／ml（95％CI：12．31～17．14），抗体浓度≥1．0μg/ml的比例为96．90％（95％CI：92．50—99．20）；对照疫苗组血清抗体GMC为22．82μg／ml（95％CI：18．44—28．25），抗体浓度≥1．0μg／ml的比例为98．55％（95％CI：92．20—99．90）。加强免疫后1个月时，实验疫苗和对照疫苗受试者血清抗体GMC分别从加强免疫前的6．27μg／ml（95％CI：5．28—7．4）和5．57μg/ml（95％CI：4．45～6．97）增加至加强免疫后1个月时的63．14μg/ml（95％CI：52．14～76．47）和73．48μg／ml（95％CI：57．37—94．11），血清抗体≥1．0μg／ml的受试者比例分别从与加强免疫前的76．35％（95％CI：68．7％-82．9％）和79．55％（95％CI：69．60-87．40）均上升至100％。加强免疫后1年时，虽两组血清抗HibPRPIgG抗体虽有下降，但GMC仍分别维持在25．02μg/ml（95％CI：20．51—30．48）和23．64μg／ml（95％CI：18．40—30．43）的较高浓度，两组的所有受试者血清抗体浓度均≥1．0μg／ml。结论实验疫苗对3—59月龄儿童能诱导产生长期保护水平的抗HibPRPtgC抗体；两种Hib结合疫苗对3～5月龄婴幼儿具有相同的免疫原性特征。

Objective To evaluate the immunogenicity of a Haemophilus influenzae type b capsular-tetanus toxoid（Hib-TT） conjugate vaccine produced by Lanzhou Institute of Biological products（LIBP）. Methods In an open-controlled, randomized trial, the eligible and consented 6-59 months-old young children injected 2 or 1 times 1 month apart with Hib-TT conjugate vaccine, the 3-5 months-old infants received 3 injections 1 month apart for primary immunization with Hib-TT or a licensed international Hib-TT conjugate vaccine as the control vaccine, and the boosting dose of two 3-5 months-old groups was injected at the 15-17 months-old. The serum anti-Hib PRP IgG GMC in both groups after primary and boosting vaccination was measured by ELISA, the percentage of geometric mean concentration （GMC） ≥ 0. 15 μg/ml and ≥ 1.0 μg/ml was calculated, respectively. Results The Hib-Tr conjugate vaccine produced in LIBP elicited satisfactory IgG antibody response in 3-59 months-old young children, the serum IgG GMC of anti-Hib PRP were 14.52 μg/ml（95% CI ： 12.31-17.14） in 3-5 months-old, 14.04 μg/ml（95% CI ： 12.40-15.90） in 6- 11 months-old, the ratios of IgG antibody concentration t〉 1.0 txg/ml were 96.90% （95% CI： 92.50- 99.20） in study vaccine group and 98.55% （95% CI： 92.20-99.90） in the control vaccine after 3 doses, respectively. 100% of the 6-11 months-old young children who injected 2 times with the Hib-TT conjugate vaccine had IgG antibody concentration ≥ 1.0 μg/ml （95% CI： 95.94-100.00）, 91.35% （95% CI： 86.13-99.48） of recipients in 12-59 months-old young children induced the IgG antibody concentration ≥ 1.0 ~g/ml after a single dose. The serum IgG antibody GMC in recipients who received the study or and control vaccines increased from 6.27 μg/ml （95% CI： 5.28-7.48） and 5.57μg/ml （95% CI： 4.45-6.97） at pre-boosting injections to 63.14 μg/ml（95% CI： 52.14-76.47） and 73.48 Ixg/ml （95% CI： 57.37- 94.11） one month after boosting injection, respectively. The percentage of IgG antibody concentration ≥1.0 μg/ml increased from 76.35% and 79.55% of pre-boosting to 100% in the two groups after booting dose. Although the serum IgG GMC in two groups appeared to decline markedly, it remained at a relatively high levels of 25.02 μg/ml （95% CI： 20.51-30.48） in the study vaccine and 23.64μg/ml （95% CI： 18.40-30.43 ） in the control vaccine, and all of the recipients in both groups remained 100.0% of IgG antibody concentration ≥ 1.0 μg/ml. Conclusion The study vaccine elicited a protective immune response and induced the IgG antibody concentration which indicated long-term protection of anti-Hib PRP in 3 to 59 months-old infants and young children.